Background HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.

Objective The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.

Methods The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.

Results The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

https://jmg.bmj.com/content/jmedgenet/early/2009/06/29/jmg.2009.069013.full.pdf

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia

Intracranial arteriovenous malformations (AVMs) are relatively uncommon but increasingly recognized lesions that can cause serious neurological symptoms or death. Although AVMs can present with hemorrhage or seizure, since the advent of contemporary brain imaging techniques, an increasing number are detected before rupture. Over the last decade, there have been significant developments in the management of intracranial AVMs. There has been an evolution of microsurgical as well as endovascular and radiosurgical techniques to treat these lesions. As the management options have evolved, individual and combined modality treatment protocols have been developed in different institutions for the management of AVMs.

A writing group was formed by the Stroke Council of the American Stroke Association to review published data for intracranial AVMs to develop practice recommendations regarding epidemiology, natural history, potential treatment strategies, and outcomes. The reports reviewed for this synthesis were selected on the basis of study design, sample size, and relevance to a particular topic. Each report was graded according to previously defined criteria.1 2 After review of the available literature, recommendations for current practice standards have been made according to 3 separate grades (Table 1⇓).

View this table:

 Table 1. 
Levels of Evidence in Grading of Recommendations for Treatment of Patients With Subarachnoid Hemorrhage



By the design of this type of review, the recommendations in this report represent an overview of existing treatment protocols that may vary considerably. These guidelines were developed to serve as a basis for the development of treatment strategies for AVMs, which overall represent a fairly heterogeneous group of cerebrovascular lesions and which may demonstrate different natural histories. In addition, for brain AVMs, no level I or II data are available in the literature. Because of the heterogeneity of these lesions and their relatively infrequent occurrence, strictly defined subcategories for comparison of the efficacy of various treatment modalities …

Recommendations for the Management of Intracranial Arteriovenous Malformations A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Stroke Association

By systematically reviewing the literature, we have found that there is very little information about the frequency and clinical course of arteriovenous malformations (AVMs) of the brain in adults because the methods of most studies have been flawed, and AVMs tend to be treated once they are discovered. The incidence of AVMs is approximately 1 per 100 000 per year in unselected populations, and the point prevalence in adults is approximately 18 per 100 000. AVMs account for between 1 and 2% of all strokes, 3% of strokes in young adults, 9% of subarachnoid haemorrhages and, of all primary intracerebral haemorrhages, they are responsible for 4% overall, but for as much as one-third in young adults. AVMs are far less common causes of first presentations with unprovoked seizures (1%), and of people presenting with headaches in the absence of neurological signs (0.3%). At the time of detection, at least 15% of people affected by AVMs are asymptomatic, about one-fifth present with seizures and for approximately two-thirds of them the dominant mode of presentation is with intracranial haemorrhage. The limited high quality data available on prognosis suggest that long-term crude annual case fatality is 1-1.5%, the crude annual risk of first occurrence of haemorrhage from an unruptured AVM is approximately 2%, but the risk of recurrent haemorrhage may be as high as 18% in the first year, with uncertainty about the risk thereafter. For untreated AVMs, the annual risk of developing de novo seizures is 1%. There is a pressing need for large, prospective studies of the frequency and clinical course of AVMs in well-defined, stable populations, taking account of their prognostic heterogeneity.

http://www.saivms.scot.nhs.uk/pdf/resPaper/Brain.pdf

A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults

http://spiral.imperial.ac.uk/bitstream/10044/1/22167/2/Shovlin.%20Blood%20Reviews%202010.pdf

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Arteriovenous malformations

Objective The vein of Galen aneurysmal malformation (VGAM) is a choroidal type of arteriovenous malformation involving the vein of Galen forerunner. This is distinct from an arteriovenous malformation with venous drainage into a dilated, but already formed, vein of Galen. Reports of endovascular treatment of VGAM in the literature approach the disease from a purely technical viewpoint and often fail to provide satisfactory midterm results. To focus the therapeutic challenge to a strictly morphological goal overlooks the fundamental aspects of neonatal and infant anatomy and fluid physiology. During the past 20 years, our approach to VGAM has remained the same. Our experience, based on 317 patients with VGAM who were studied in Hospital Bicetre between October 1981 and October 2002, allows us to describe the angioarchitecture, natural history, and management of VGAM in neonates, infants, and children. Methods Of our cohort of 317 patients, 233 patients were treated with endovascular embolization; of these, 216 patients were treated in our hospital. The treatment method of choice was a transfemoral arterial approach to deliver glue at the fistulous zone. Results Of 216 patients, 23 died despite or because of the embolization (10.6%). Twenty out of the 193 (10.4%) surviving patients were severely retarded, 30 (15.6%) were moderately retarded, and 143 (74%) were neurologically normal on follow-up. Conclusion Our data demonstrate that most treated children survive and undergo normal neurological development; an understanding of the clinical, anatomical, and pathophysiological features of VGAM has, therefore, reversed the former poor prognosis. Our level of understanding about the lesion allows us to predict most situations and remedy them by applying a strict evaluation protocol and working within an optimal therapeutic window. Patient selection and timing remain the keys in the management of this condition. It is more important to restore normal growth conditions than a normal morphological appearance, with the primary therapeutic objective being normal development in a child without neurological deficit.

The management of vein of Galen aneurysmal malformations.

Objective
The objective was to review the clinical aspects and therapeutic strategies in a series of aneurysmal vasculopathies seen in children 15 years or under

Intracranial aneurysms in children aged under 15 years: review of 59 consecutive children with 75 aneurysms.

OBJECTIVE: Spinal cord arteriovenous shunts (SCAVSs) are currently classified according to their morphological features. Certain shunts cannot be fully integrated into the predetermined categories that are usually described, however. Can these classifications be reevaluated on the basis of recent anatomic, biological, and genetic advances? METHODS: We reviewed the clinical and radiological files for 155 SCAVSs that were treated at Hopital Bicetre between 1981 and 1999. The lesions were examined with respect to their number (single or multiple), their primary architectural type (nidus or fistula), and their possible links with associated metameric lesions. RESULTS: All SCAVSs were either arteriovenous malformations or fistulae, with the latter being either micro- or macrofistulae. All SCAVSs corresponded to three categories, i.e., genetic hereditary lesions (macrofistulae and hereditary hemorrhagic telangiectasia), genetic nonhereditary lesions (all of which were multiple lesions with metameric or myelomeric associations), and single lesions (which could represent incomplete presentations of one of the previous groups). Of the SCAVSs in our series, 81% were single lesions and 19% were multiple; among these, 59% were true intradural shunts with metameric features. Ten cases of Cobb syndrome, three cases of Klippel-Trenaunay syndrome, and two cases of Parkes-Weber syndrome, all with associated cord lesions, were observed. Nineteen percent of SCAVSs were fistulae; 23% of those were macrofistulae, of which 83% were related to Rendu-Osler-Weber disease. CONCLUSION: It seems legitimate to propose a categorization that takes into consideration a primary malformation (nidus or fistula) that evolves with time and in which angioarchitectural changes occur. Recognition of the factors originally responsible for the shunt (e.g., genetic hereditary or genetic nonhereditary) allows a different classification of SCAVSs.

Classification of spinal cord arteriovenous shunts: proposal for a reappraisal--the Bicêtre experience with 155 consecutive patients treated between 1981 and 1999.

Over the past 10 years (1982-1992), we have been actively involved in the management of 179 cerebral arteriovenous malformations (CAVMs) in children and infants. Seventy-seven were true vein of Galen malformations (VGAMs) and 102 were pial AVMs (PAVMs), i.e., developed in the subpial space. Hemorrhage occurred as the first symptom in 50% of the children with pial AVMs, but was present in none of the VGAM cases. Only 31 children were found to be unsuitable for endovascular treatment, and in 124 cases embolization was indicated as the primary treatment (104 embolization performed). Only 21 children underwent a direct surgical approach (none in the VGAM group). In the embolized group in whom treatment has been completed (n = 56), 8 children died, 39 have an anatomical cure, and 34 are clinically normal. In the group under treatment (n = 48), 16 are not normal. The problems are timing and the aims (total or partial treatment) of the therapeutic procedures. In the nonembolized group (n = 31), 8/13 of the pial lesions were operated on (no mortality, 2 patients with moderate neurological deficits). In the VGAM group 13/18 died and 4 had spontaneous thrombosis (only 1 is neurologically normal). In the nonembolized group 13 lesions have been completely excluded, but only 5 patients are neurologically normal. This fact again stresses the need for prognostic evaluation before treatment and a clear definition of the treatment aims. Analysis of a large number of published series on the management of children with AVMs (1017 cases) reveals inconsistencies that hamper proper evaluation and comparison. In our experience, endovascular treatment always seems to be the best primary treatment in both VGAMs and PAVMs. However, management of children with these lesions requires a large multidisciplinary team, which is the only way of offering the most suitable and effective treatment, the sole guarantee of a good result.

Cerebral arteriovenous malformations in children. Management of 179 consecutive cases and review of the literature

Cerebral vasculitis is characterized by inflammation of the walls of blood vessels and may affect vessels of any size. The pathogenesis of vasculitis remains poorly understood. Vasculitis may affect large vessels (Takayasu arteritis, giant cell arteritis), medium-sized vessels (Kawasaki disease, polyarteritis nodosa), small vessels (immunoglobulin A vasculitis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis), or variable-sized vessels (Behcet disease, Cogan syndrome). Primary angiitis of the central nervous system (CNS) is an idiopathic disorder with no evidence of generalized inflammation that may simulate reversible cerebral vasoconstriction syndromes. Vasculitis may be secondary to systemic disease, infection, malignancy, drug use, or radiation therapy. Imaging findings vary from small ischemic changes to frank infarction, hemorrhage, and white matter edema and may show contrast material enhancement. The cerebral arteries may demonstrate a beaded appearance with variable degrees of stenosis, occlusion, and contrast enhancement of the vessel wall. Correlation of imaging findings with clinical presentation and laboratory test results helps establish the diagnosis of CNS vasculitis.

https://pubs.rsna.org/doi/pdf/10.1148/rg.344135028

Hortensia Alvarez

Papers

The management of vein of Galen aneurysmal malformations.

Intracranial aneurysms in children aged under 15 years: review of 59 consecutive children with 75 aneurysms.

Classification of spinal cord arteriovenous shunts: proposal for a reappraisal--the Bicêtre experience with 155 consecutive patients treated between 1981 and 1999.

Cerebral arteriovenous malformations in children. Management of 179 consecutive cases and review of the literature

Imaging Spectrum of CNS Vasculitis